Oxidative stress and ageing: Is ageing a cysteine deficiency syndrome?

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 360, Issue 1464, 2005, Pages 2355-2372

  Dröge, Wulf ^a  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Cysteine in vivo; Immune functions; Inflammatory cytokines; Insulin signalling; Muscle functions; Redox status

Indexed keywords

AGING; AMINO ACID; BODY CONDITION; FREE RADICAL; HORMONE; IMMUNE RESPONSE; MUSCLE; MUTATION; OXYGEN; PHYSIOLOGICAL RESPONSE; REDOX CONDITIONS; SIGNAL;

MUS;

CYSTEINE; GLUTATHIONE; INSULIN RECEPTOR; PROTEIN TYROSINE PHOSPHATASE; REACTIVE OXYGEN METABOLITE; SERUM ALBUMIN; TUMOR NECROSIS FACTOR ALPHA;

AGING; BLOOD; BODY COMPOSITION; CELLULAR IMMUNITY; CHEMISTRY; DIET SUPPLEMENTATION; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; METABOLISM; OXIDATIVE STRESS; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE;

AGING; BODY COMPOSITION; CYSTEINE; DIETARY SUPPLEMENTS; GLUTATHIONE; HUMANS; IMMUNITY, CELLULAR; MUSCLE, SKELETAL; OXIDATIVE STRESS; PROTEIN-TYROSINE-PHOSPHATASE; REACTIVE OXYGEN SPECIES; RECEPTOR, INSULIN; SERUM ALBUMIN; SIGNAL TRANSDUCTION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 33745247801     PISSN: 09628436     EISSN: None     Source Type: Journal    
DOI: 10.1098/rstb.2005.1770     Document Type: Conference Paper

References (163)

1. Acharyya, S., Ladner, K. J., Nelsen, L. L., Damrauer, J., Reiser, P. J., Swoap, S. & Guttridge, D. C. 2004 Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J. Clin. Invest. 114, 370-378. (doi:10.1172/JCI200420174.)
2. Arivazhagan, P., Ramanathan, K. & Panneerselvam, C. 2001 Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem. Biol. Interact. 138, 189-198. (doi:10.1016/S0009-2797(01)00268-X.)
3. Azzoni, L., Papasawas, E., Chehimi, J., Kostman, J. R., Mounzer, K., Ondercin, J., Perussia, B. & Montaner, L. J. 2002 Sustained impairment of IFN-γ secretion in suppressed HIV-infected patients despite mature NK cell recovery: evidence for a defective reconstitution of innate immunity. J. Immunol. 168, 5764-5770.
4. Balkan, J., Kanbagli, O., Mehmetcik, G., Mutlu-Turkoglu, U., Aykac-Toker, G. & Uysal, M. 2002 Increased lipid peroxidation in serum and low-density lipoproteins associated with aging in humans. Int. J. Vitam. Nutr. Res. 72, 315-320.
5. Barford, D., Jia, Z. & Tonks, N. K. 1995 Protein tyrosine phosphatases take off. Nat. Struct. Biol. 2, 1043-1053. (doi:10.1038/nsb1295-1043.)
6. Barrett, W. C., DeGnore, J. P., Keng, Y.-F., Zhang, Z.-Y., Yim, M. B. & Chock, P. B. 1999a Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B. J. Biol. Chem. 274, 34 543-34 546. (doi:10.1074/jbc.274.49. 34543.)
7. Barrett, W. C., DeGnore, J. P., Konig, S., Fales, H. M., Keng, Y.-F., Zhang, Z.-Y., Yim, M. B. & Chock, P. B. 1999b Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry 38, 6699-6705. (doi:10.1021/bi990240v.)
8. Bartfay, W. J., Davis, M. T., Medves, J. M. & Lugowski, S. 2003 Milk whey protein decreases oxygen free radical production in a murine model of chronic iron-overload cardiomyopathy. Can. J. Cardiol. 19, 1163-1168.
9. Bates, C. J., Manssor, M. A., Gregory, J., Pentieva, K. & Prentice, A. 2002 Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of Young People Aged 4-18 years, and a comparison with the Survey of People Aged 65 Years and Over. Br. J. Nutr. 87, 71-79. (doi:10.1079/BJN2001479.)
10. Baumgartner, R. N., Koehler, K. M., Romero, L. & Garry, P. J. 1996 Serum albumin is associated with skeletal muscle in elderly men and women. Am. J. Clin. Nutr. 64, 552-558.
11. Beckman, K. B. & Ames, B. N. 1998 The free radical theory of aging matures. Physiol. Rev. 78, 547-581.
12. Blair, S. N., Kohl III, H. W., Paffenbarger Jr, R. S., Clark, D. G., Cooper, K. H. & Gibbons, L. W. 1989 Physical fitness and all-cause mortality. A prospective study of healthy men and women. J. Am. Med. Assoc. 262, 2395-2401. (doi:10.1001/jama.262.17.2395.)
13. Blair, S. N., Kohl III, H. W., Barlow, C. E., Paffenbarger Jr, R. S., Gibbons, L. W. & Macera, C. A. 1995 Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men. J. Am. Med. Assoc. 273, 1093-1098. (doi:10.1001/jama.273.14.1093.)
14. Bluher, M., Kahn, B. B. & Kahn, C. R. 2003 Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299, 572-574. (doi:10.1126/science.1078223.)
15. Bois, P. R. J. & Grosveld, G. C. 2003 FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts. EMBO J. 22, 1147-1157. (doi:10.1093/emboj/cdg116.)
16. Bounous, G. & Gold, P. 1991 The biological activity of undenatured dietary whey proteins: role of glutathione. Clin. Invest. Med. 14, 296-309.
17. Bounous, G. & Kongshaven, P. A. 1982 Influence of dietary proteins on the immune system of mice. J. Nutr. 112, 1747-1755.
18. Bounous, G., Letourneau, L. & Kongshaven, P. A. 1983 Influence of dietary proteins on the immune system of mice. J. Nutr. 113, 1415-1421.
19. Bouthegourd, J.-C. J., Roseau, S. M., Makarios-Lahham, L., Leruyet, P. M., Tomé, D. G. & Even, P. C. 2002 A preexercise α-lactalbumin- enriched whey protein meal preserves lipid oxidation and decreases adiposity in rats. Am. J. Physiol. Endocrinol. Metab. 283, E565-E572.
20. Brattström, L., Lindgren, A., Israelsson, B., Andersson, A. & Hultberg, B. 1994 Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. J. Intern. Med. 236, 633-641.
21. Breitkreutz, R., Holm, S., Pittak, N., Beichert, M., Babylon, A., Yodoi, J. & Dröge, W. 2000a Massive loss of sulfur in HIV infection. AIDS Res. Hum. Retroviruses 16, 203-209. (doi:10.1089/ 088922200309296.)
22. Breitkreutz, R. et al. 2000b Imrovement of immune functions in HIV infection by sulfur supplementation-two randomized trials. J. Mol. Med. 78, 55-62. (doi:10.1007/s001090050382.)
23. Brunet, A. et al. 1999 Akt promotes cell survival by phosphorylating and inhibiting a Fork-head transcription factor. Cell 96, 857-868. (doi:10.1016/S0092-8674(00)80595-4.)
24. Bruunsgaard, H., Andersen-Ranberg, K., Jeune, B., Pedersen, A. N., Skinhoj, P. & Pedersen, B. K. 1999 A high plasma concentration of TNF-a is associated with dementia in centenarians. J. Gerontol. Med. Sci. 54A, M357-M364.
25. Bruunsgaard, H., Skinhøj, P., Pedersen, A. N., Schroll, M. & Pedersen, B. K. 2000 Ageing, TNF-α and atherosclerosis. Clin. Exp. Immunol. 21, 255-260. (doi:10.1046/j.1365-2249.2000.01281.x.)
26. Bruunsgaard, H., Pedersen, M. & Pedersen, B. K. 2001 Aging and proinflammatory cytokines. Curr. Opin. Hematol. 8, 131-136. (doi:10.1097/00062752-200105000-00001.)
27. Bruunsgaard, H., Andersen-Ranberg, K., Hjelmborg, J. V. B., Pedersen, B. K. & Jeune, B. 2003 Elevated levels of tumor necrosis factor-α and mortality in centenarians. Am. J. Med. 115, 278-283. (doi:10.1016/S0002-9343(03)00329-2.)
28. Buchner, D. M. & Wagner, E. H. 1992 Preventing frail health. Clin. Geriatr. Med. 8, 1-17.
29. Buchner, D. M., Cress, M. E., DeLateur, B. J., Esselman, P. C., Margherita, A. J., Price, R. & Wagner, E. H. 1997 The effect of strength and endurance on gait, balance, fall risk, and health services use in community-living older adults. J. Gerontol. A Biol. Sci. Med. Sci. 52A, M218-M224.
30. Bukowski, J. F., Warner, J. F., Dennert, G. & Welsh, R. M. 1985 Adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo. J. Exp. Med. 161, 40-52. (doi:10.1084/jem.161.1.40. )
31. Cakatay, U., Telci, A., Kayali, R., Tekeli, F., Akcay, T. & Sivas, A. 2003 Relation of aging with oxidative protein damage prameters in the rat skeletal muscle. Clin. Biochem. 36, 51-55. (doi:10.1016/S0009- 9120(02)00407-1.)
32. Cantin, A. M., Paquette, B., Richter, M. & Larivée, P. 2000 Albumin-mediated regulation of cellular glutathione and nuclear factor kappa B activation. Am. J. Respir. Crit. Care Med. 162, 1539-1546.
33. Carlsson, P. & Mahlapuu, M. 2002 Forkhead transcription factors: key players in development and metabolism. Dev. Biol. 250, 1-23. (doi:10.1006/dbio.2002.0780.)
34. Chandler, J. M. & Hadley, E. C. 1996 Exercise to improve physiologic and functional performance in old age. Clin. Geriatr. Med. 12, 761-784.
35. De Cabo, R., Cabello, R., Rios, M., López-Lluch, G., Ingram, D. K., Lane, M. A. & Navas, P. 2004 Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver. Exp. Gerontol. 39, 297-304. (doi:10.1016/j.exger.2003.12.003.)
36. Demling, R. H. &. DeSanti, L. 2000 Effect of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers. Ann. Nutr. Metab. 44, 21-29. (doi:10.1159/000012817.)
37. Denu, J. M. & Tanner, K. G. 1998 Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry 37, 5633-5642. (doi:10.1021/bi973035t.)
38. Dorman, J. B., Albinder, B., Shroyer, T. & Kenyon, C. 1995 The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics 141, 1399-1406.
39. Dröge, W. & Holm, E. 1997 Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. FASEB J. 11, 1077-1089.
40. Dröge, W. 2002a Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47-95.
41. Dröge, W. 2002b Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp. Gerontol. 37, 1333-1345. (doi:10.1016/S0531-5565(02)00175-4.)
42. Dröge, W. 2002c The plasma redox state and ageing. Ageing Res. Rev. 1, 257-278.
43. Dröge, W. 2003 Autophagy and aging - importance of amino acid levels. Mech. Ageing Dev. 125, 161-168. (doi:10.1016/j.mad.2003. 12.003.)
44. Eck, H.-P., Gmünder, H., Hartmann, M., Petzoldt, D., Daniel, V. & Dröge, W. 1989 Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1 infected patients. Biol. Chem. Hoppe-Seyler 370, 101-108.
45. Erden-Inal, M., Sunal, E. & Kanbak, G. 2002 Age-related chnages in the glutathione redox system. Cell Biochem. Funct. 20, 61-66. (doi:10.1002/cbf.937.)
46. Fiatarone, M. A. et al. 1994 Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl. J. Med. 330, 1769-1775. (doi:10.1056/NEJM199406233302501.)
47. Fillit, H., Ding, W. H., Buee, L. et al. 1991 Elevated circulating tumor necrosis factor levels in Alzheimer's disease. Neurosci. Lett. 129, 318-320. (doi:10.1016/0304-3940(91)90490-K.)
48. Fraga, C. G., Shigenaga, M. K., Park, J. W., Degan, P. & Ames, B. N. 1990 Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc. Natl Acad. Sci. USA 87, 4533-4537.
49. Furukawa, T., Meydani, S. N. & Blumberg, J. B. 1987 Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech. Ageing Dev. 38, 107-117. (doi:10.1016/0047-6374(87)90071-6.)
50. Furuke, K., Shiraishi, M., Mostowski, H. S. & Bloom, E. T. 1999 Fas ligand induction in human NK cells is regulated by redox through a calcineurin-nuclear factors of activated T cell-dependent pathway. J. Immunol. 162, 1988-1993.
51. Gaiter, D., Mihm, S. & Dröge, W. 1994 Distinct effects of glutathione disulphide on the nuclear transcription factor kappa B and the activator protein-1. Eur. J. Biochem. 221, 639-648. (doi:10.1111/j.1432-1033.1994.tb18776.x.)
52. Gozuacik, D. & Kimchi, A. 2004 Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23, 2891-2906. (doi:10.1038/sj.onc. 1207521.)
53. Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F. & Karin, M. 2004 IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118, 285-296. (doi:10.1016/j.cell.2004.07.013.)
54. Guarente, L. & Kenyon, C. 2000 Genetic pathways that regulate ageing in model organisms. Nature 408, 255-262. (doi:10.1038/35041700.)
55. Guralnik, J. M., Simonsick, E. M., Ferucci, L., Glynn, R. J., Berkman, L. F., Blazer, D. G., Scherr, P. A. & Wallace, R. B. 1994 A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J. Gerontol. 49, M85-M94.
56. Guttridge, D. C., Mayo, M. W., Madrid, L. V., Wang, C. Y. & Baldwin Jr, A. S. 2000 NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 289, 2363-2366. (doi:10.1126/science.289.5488.2363.)
57. Hack, V., Breitkreutz, R., Kinscherf, R., Röhrer, H., Bärtsch, P., Taut, F., Benner, A. & Dröge, W. 1998 The redox state as a correlate of senescence and wasting and as a target for therapeutic intervention. Blood 92, 59-67.
58. Haj, F. G., Verveer, P. J., Squire, A., Neel, B. G. & Bastiaens, P. I. 2002 Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science 295, 1708-1711. (doi:10.1126/science.1067566.)
59. Halliwell, B. & Gutteridge, M. C. 1990 The antioxidants of human extracellular fluids. Arch. Biochem. Biophys. 280, 1-8. (doi:10.1016/0003-9861(90)90510-6.)
60. Hansson, M., Asea, A., Ersson, U., Hermodsson, S. & Hellstrand, K. 1996 Induction of apoptosis in NK cells by monocyte-derived reactive oxygen metabolites. J. Immunol. 156, 42-47.
61. Harman, D. 1956 Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11, 298-300.
62. Harman, D. 1981 The aging process. Proc. Natl Acad. Sci. USA 78, 7124-7128.
63. Hauer, K., Rost, B., Rütschle, K., Opitz, H., Specht, N., Bartsch, P., Oster, P. & Schlierf, G. 2001 Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls. J. Am. Geriatr. Soc. 49, 10-20. (doi:10.1046/j.1532-5415. 2001.49004.x.)
64. Hauer, K., Hildebrandt, W., Sehl, Y., Edler, L., Oster, P. & Dröge, W. 2003 Improvement in muscular performance and decrease in tumor necrosis factor level in old age after antioxidant treatment. J. Mol. Med. 81, 118-125.
65. Hehner, S. P., Breitkreutz, R., Shubinsky, G., Unsoeld, H., Schulze-Osthoff, K., Schmitz, M. L. & Dröge, W. 2000 Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol pool. J. Immunol. 165, 4319-4328.
66. Hekimi, S. & Guarente, L. 2003 Genetics and the specificity of the aging process. Science 299, 1351-1354. (doi:10.1126/science. 1082358.)
67. Hernanz, A., Fernández-Vivancos, E., Montiel, C., Vazquez, J. J. & Arnalich, F. 2000 Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci. 67, 1317-1324. (doi:10.1016/S0024-3205(00)00722-0.)
68. Herzenberg, L. A., De Rosa, R. S., Dubs, J. G., Roederer, M., Anderson, M. T., Ela, S. W., Deresinski, S. C. & Herzenberg, L. A. 1997 Glutathione deficiency is associated with impaired survival in HIV disease. Proc. Natl Acad. Sci. USA 94, 1967-1972. (doi:10.1073/pnas.94.5.1967.)
69. 2-chemosensitivity. Blood 99, 1552-1555. (doi:10.1182/blood.V99.5.1552.)
70. Hildebrandt, W., Kinscherf, R., Hauer, K., Holm, E. & Dröge, W. 2002b Plasma cysteine concentration and redox state in ageing and physical exercise. Mech. Ageing Dev. 123, 1269-1281. (doi:10.1016/S0047-6374(02)00013-1.)
71. Hildebrandt, W. et al. 2004 Effect of thiol antioxidant on body fat and insulin reactivity. J. Mol. Med. 82, 336-344. (doi:10.1007/s00109-004-0532-5.)
72. Honda, Y. & Honda, S. 1999 The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 13, 1385-1393.
73. Hribal, M. L., Nakae, J., Kitamura, T., Shutter, J. R. & Accili, D. 2003 Regulation of insulin-like growth factor-dependent myoblast differentiation by Foxo forkhead transcription factors. J. Cell Biol. 162, 535-541. (doi:10.1083/jcb.200212107.)
74. Inal, M. E., Kanbak, G. & Sunal, E. 2001 Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin. Chim. Acta 305, 75-80. (doi:10.1016/S0009-8981(00)00422-8.)
75. Jacob, N., Bruckert, E., Giral, P., Foglietti, M. J. & Turpin, G. 1999 Cysteine is a cardiovascular risk factor in hyperlipidemic patients. Atherosclerosis 146, 53-59. (doi:10.1016/S0021-9150(99)00128-8.)
76. Jones, D. P., Carlson, J. L., Mody Jr, V. C., Cai, J., Lynn, M. J. & Sternberg Jr, P. 2000 Redox state of glutathione in human plasma. Free Radic. Biol. Med. 28, 625-635. (doi:10.1016/S0891-5849(99)00275-0.)
77. Kasapoglu, M. & Ozben, T. 2001 Alterations of antioxidant enzymes and oxidative stress markers in aging. Exp. Gerontol. 36, 209-220. (doi:10.1016/S0531-5565(00)00198-4.)
78. Kenyon, C., Chang, J., Gensch, E., Rudner, A. & Tabtlang, R. 1993 A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464. (doi:10.1038/366461a0.)
79. Kim, S., Iizuka, K., Aguila, H. L., Weissman, I. L. & Yokoyama, W. M. 2000 In vivo natural killer cell activities revealed by natural killer cell-deficient mice. PNAS 97, 2731-2736. (doi:10.1073/pnas. 050588297.)
80. Kimura, K. D., Tissenbaum, H. A., Liu, Y. & Ruvkun, G. 1997 daf-2, an insulin receptor-like gene that regulates longevity and diapuase in Caenorhabditis elegans. Science 277, 942-946. (doi:10.1126/ science.277.5328.942.)
81. + cells. FASEB J. 8, 448-451.
82. Kinscherf, R., Hack, V., Fischbach, T., Friedmann, B., Weiss, C., Edler, L., Bartsch, P. & Dröge, W. 1996 Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine. J. Mol. Med. 74, 393-400. (doi:10.1007/s001090050040.)
83. Kirkwood, T. B. L. 1996 Human senescence. BioEssays 18, 1009-1016. (doi:10.1002/bies.950181211.)
84. Klionsky, D. J. & Emr, S. D. 2000 Autophagy as a regulated pathway of cellular degradation. Science 290, 1717-1721. (doi:10.1126/science.290.5497.1717.)
85. Kono, K., Slazar-Onfray, F., Petersson, M., Hansson, J., Masucci, G., Wasserman, K., Nakazawa, T., Anderson, P. & Kiessling, R. 1996 Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell and natural killer cell-mediated cytotoxicity. Eur. J. Immunol. 26, 1308-1313.
86. Kops, G. J. P. L. et al. 2002 Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419, 316-321. (doi:10.1038/nature01036.)
87. Kuge, S. & Jones, N. 1994 YAP-1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides. EMBO J. 13, 655-664.
88. Kumaran, S., Deepak, B., Naveen, B. & Panneerselvam, C. 2003 Effects of levocarnitine on mitochondrial antioxidant systems and oxidative stress in aged rats. Drugs R&D 4, 141-147.
89. Kuwata, K., Era, S. & Sogami, M. 1994 The kinetic studies on the intracellular SH, S-S exchange reaction of bovine mercaptalbumin. Biochim. Biophys. Acta 1205, 317-324.
90. Lands, L. C., Grey, V. L. & Smountas, A. A. 1999 Effect of supplementation with a cysteine donor on muscular performance. J. Appl. Physiol. 87, 1381-1385.
91. Larsen, P. L., Albert, P. S. & Riddle, D. I. 1995 Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139, 1567-1583.
92. Lee, C. K., Klopp, R. G., Weindruch, R. & Prolla, T. A. 1999 Gene expression profile of aging and its retardation by caloric restriction. Science 285, 1390-1393. (doi:10.1126/science.285.5432.1390.)
93. 2. J. Biol. Chem. 277, 20 336-20 342. (doi:10.1074/jbc.M111899200.)
94. Lemon, K. J., Therriault, H., Cantin, A. M., Fulop, T., Payette, H. & Wagner, J. R. 2000 Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. Am. J. Clin. Nutr. 71, 1194-1200.
95. Levine, R. L. & Stadtman, E. R. 2001 Oxidative modification of proteins during aging. Exp. Gerontol. 36, 1495-1502. (doi:10.1016/S0531-5565(01)00135-8.)
96. Lin, Y.-J., Seroude, L. & Benzer, S. 1998 Extended life-span and stress resistance in the drosophila mutant methuselah. Science 282, 943-946. (doi:10.1126/science.282.5390.943.)
97. Longo, V. D. & Finch, C. E. 2003 Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299, 1342-1346. (doi:10.1126/science.1077991.)
98. Low, P. P. L., Rutherfurd, K. J., Gill, H. S. & Cross, M. L. 2003 Effect of dietary whey protein concentrate on primary and secondary antibody responses in immunized BALB/cmice. Int. Immunopharmacol. 3, 393-401. (doi:10.1016/S1567-5769(02)00297-7.)
99. Lucas, D. T. & Szweda, L. I. 1998 Cardiac reperfusion injury: aging, lipid peroxidation, and mitochondrial dysfunction. Proc. Natl Acad. Sci. USA 95, 510-514. (doi:10.1073/pnas.95.2.510.)
100. Mantovani, G., Madeddu, C., Macciò, A., Gramignano, G., Lusso, M. R., Massa, E., Astara, G. & Serpe, R. 2004 Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment. Cancer Epidemiol. Biomarkers Prev. 13, 1651-1659.
101. Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F. & Turner, R. C. 1985 Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412-419. (doi:10.1007/BF00280883.)
102. McKinnell, I. W. & Rudnicki, M. A. 2004 Molecular mechanisms of muscle atrophy. Cell 119, 907-910. (doi:10.1016/j.cell.2004.12. 007.)
103. Meister, A. & Anderson, M. E. 1983 Glutathione. Annu. Rev. Biochem. 52, 711-760. (doi:10.1146/annurev.bi.52.070183.003431.)
104. Melendez, A., Talloczy, Z., Seaman, M., Eskelinen, E. L., Hall, D. H. & Levine, B. 2003 Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387-1391. (doi:10.1126/science.1087782.)
105. Middleton, N., Jelen, P. & Bell, G. 2004 Whole blood and mononuclear cell glutathione response to dietary whey protein supplementation in sedentary and trained male human subjects. Int. J. Food Sci. 55, 131-141. (doi:10.1080/096374080410001666504.)
106. shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313. (doi:10.1038/46311.)
107. Mihm, S., Ennen, J., Pessara, U., Kurth, R. & Dröge, W. 1991 Inhibition of HIV-1 replication and NFkB activity by cysteine and cysteine derivatives. AIDS 5, 497-503.
108. Morris, J. Z., Tissenbaum, H. A. & Ruvkun, G. 1996 A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382, 536-539. (doi:10.1038/382536a0.)
109. Murphy, C. T., McCarroll, S. A., Bargmann, C. I., Fraser, A., Kamath, R. S., Ahringer, J., Li, H. & Kenyon, C. 2004 Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277-284. (doi:10.1038/nature01789.)
110. Nemoto, S. & Finkel, T. 2004 Ageing and the mystery at Aries. Nature 429, 149-152. (doi:10.1038/429149a.)
111. Nuttall, S. L., Martin, U., Sinclair, A. J. & Kendall, M. J. 1998 Glutathione: in sickness and in health. The Lancet 351, 645-646. (doi:10.1016/S0140-6736(05)78428-2.)
112. Oldham, S. & Hafen, E. 2003 Insulin/IGF and target of rapamycin signlaing: a TOR de force in growth control. Trends Cell Biol. 13, 79-85. (doi:10.1016/S0962-8924(02)00042-9.)
113. Orr, W. C. & Sohal, R. S. 1994 Extension of lifespan by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263, 1128-1130.
114. Oubidar, M., Boquillon, M., Marie, C., Bouvier, C., Beley, A. & Bralet, J. 1996 Effect of intracellular iron loading on lipid peroxidation of brain slices. Free Radic. Biol. Med. 21, 763-769. (doi:10.1016/0891-5849(96)00173-6.)
115. Paasche, G., Huster, D. & Reichenbach, A. 1998 The glutathione content of retinal Muller (glial) cells: the effects of aging and of application of free-radical scavengers. Ophthalmic Res. 30, 351-360. (doi:10.1159/000055495.)
116. Pallardó, F. V., Asensi, M., Garcia de la Asuncion, J., Anton, V., Lloret, A., Sastre, J. & Vina, J. 1999 Late onset administration of oral antioxidants prevents age-related loss of motor co-ordination and brain mitochondrial DNA damage. Free Radic. Res. 29, 617-623.
117. Paradis, S., Ailion, M., Toker, A., Thomas, J. H. & Ruvkun, G. A. 1999 PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev. 13, 1438-1452.
118. Parker, N. T. & Goodrum, K. J. 1990 A comparison of casein, lactalbumin, and soy protein effect on the immune response to a T-dependent antigen. Nutr. Res. 10, 781-792.
119. Parkes, T. L., Elia, A. J., Dickinson, D., Hilliker, A. J., Boulianne, G. L. & John, P. 1998 Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat. Genet. 19, 171-174. (doi:10.1038/534.)
120. Paterson, R. L., Galley, H. F. & Webster, N. R. 2003 The effect of N-acetylcysteine on nuclear factor-κB activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit. Care Med. 31, 2574-2578. (doi:10.1097/01.CCM. 0000089945.69588.18.)
121. Peters Jr, T. 1985 Serum albumin. Adv. Protein Chem. 37, 161-245.
122. Pikarsky, E. et al. 2004 NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461-466. (doi:10.1038/nature02924.)
123. Rager-Zisman, B., Quan, P. C., Rosner, M., Moller, J. R. & Bloom, B. R. 1987 Role of NK cells in protection of mice against herpes simplex virus-1 infection. J. Immunol. 138, 884-888.
124. Rantanen, T., Harris, T., Leville, S. G., Visser, M., Foley, D., Masdaki, K. & Guarlnik, J. M. 2000 Muscle strength and body mass index as long term predictors for mortality in initially healthy men. J. Gerontol. 55, M168-M173.
125. Roth, S. & Dröge, W. 1987 Regulation of T cell activation and T cell growth factor (TCGF) production by hydrogen peroxide. Cell. Immunol. 108, 417-424. (doi:10.1016/0008-8749(87)90224-3.)
126. Rothschild, M. A., Oratz, M. & Schreiber, S. S. 1988 Serum albumin. Hepatology 8, 385-401.
127. Rukavina, D., Laskarin, G., Rubesa, G., Strbo, N., Bedenicki, I., Manestar, D., Glavas, M., Christmas, S. E. & Podack, E. R. 1998 Age-related decline of perforin expression in human cytotoxic T lymphocytes and natural killer cells. Blood 92, 2410-2420.
128. Sacheck, J. M., Ohtsuka, A., McLary, C. & Goldberg, A. L. 2004 IGF-1 stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am. J. Physiol. Endocrinol. Metab. 287, E591-E601. (doi:10.1152/ajpendo.00073.2004.)
129. Salmeen, A., Andersen, J. N., Myers, M. P., Meng, T.-C., Hinks, J. A., Tonks, N. K. & Barford, D. 2003 Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423, 769-773. (doi:10.1038/nature01680.)
130. Samiec, P. S., Drews-Botsch, C., Flagg, E. W., Kurtz, J. C., Sternberg Jr, P., Reed, R. L. & Jones, D. P. 1998 Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radic. Biol. Med. 24, 699-704. (doi:10.1016/S0891-5849(97) 00286-4.)
131. Sandri, M. et al. 2004 Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 111, 399-412. (doi:10.1016/S0092-8674(04)00400-3.)
132. Sandvik, L., Erikssen, J., Thaulow, E., Erikssen, G., Mundal, R. & Rodahl, K. 1993 Physical fitness as a predictor of mortality among healthy, middle-aged Norwegian men. N. Engl. J. Med. 328, 533-537. (doi:10.1056/NEJM199302253280803.)
133. Sasaki, T., Senda, M., Kim, S., Kojima, S. & Kubodera, A. 2001 Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain. Nucl. Med. Biol. 28, 25-31. (doi:10.1016/S0969-8051(00)00180-3.)
134. Sato, H., Tamba, M., Ishii, T. & Bannai, S. 1999 Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J. Biol. Chem. 274, 11 455-11 458. (doi:10.1074/jbc.274.17.11455.)
135. Scalzo, A. A. 2002 Successful control of viruses by NK cells - a balance of opposing forces? Trends Microbiol. 10, 470-474. (doi:10.1016/S0966-842X(02)02441-1.)
136. Schmid, E., El Benna, J., Gaiter, D., Klein, G. & Dröge, W. 1998 Redox priming of the insulin receptor b-chain associated with altered tyrosine kinase activity and insulin responsiveness in the absence of tyrosine autophosphorylation. FASEB J. 12, 863-870.
137. Schmitt, T. L., Hotz-Wagenblatt, A., Klein, H. & Dröge, W. 2005 Interdependent regulation of insulin receptor kinase activity by ADP and hydrogen peroxide. J. Biol. Chem. 280, 3795-3801. (doi:10.1074/jbc.M410352200.)
138. Schreck, R. & Baeuerle, P. A. 1991 Reactive oxygen intermediates as apparently widely used messengers in the activation of NF-κB transcription factor and HIV-1. Trends Cell Biol. 1, 39-42. (doi:10.1016/0962-8924(91)90072-H.)
139. Scrofano, M. M. et al. 1998 The effects of aging and calorie restriction on plasma nutrient levels in male and female emory mice. Mech. Ageing Dev. 105, 31-44. (doi:10.1016/S0047-6374(98)00077-3.)
140. Shao, Y., Gao, Z., Marks, P. A. & Jiang, X. 2004 Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. PNAS 101, 18 030-18 035. (doi:10.1073/pnas.0408345102.)
141. Shibata, H., Haga, H., Ueno, M., Nagai, H., Yasumura, S. & Koyano, W. 1991 Longitudinal changes of serum albumin in elderly people living in the community. Age Aging 20, 417-420.
142. Sies, H. 1999 Glutathione and its role in cellular functions. Free Radic. Biol. Med. 27, 916-921. (doi:10.1016/S0891-5849(99)00177-X.)
143. Solomon, A. & Goldberg, A. 1996 Importance of the ATP-ubiquitin-proteasome pathway in the degradation of soluble and myofibrillar proteins in rabbit muscle extracts. J. Biol. Chem. 271, 26 690-26 697. (doi:10.1074/jbc.271.41.25240.)
144. Staal, F. J. T., Roederer, M., Herzenberg, L. A. & Herzenberg, L. A. 1990 Intracellular thiols regulate activation of nuclear factor κB and transcription of human immunodeficiency virus. Proc. Natl Acad. Sci. USA 87, 9943-9947.
145. Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D. & Glass, D. J. 2004 The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell 14, 395-403. (doi:10.1016/S1097-2765(04)00211-4.)
146. Tahir, S. M. A., Cheng, O., Shaulov, A., Koezuka, Y., Bubley, G. J., Wilson, S. B., Balk, S. P. & Exley, M. A. 2001 Loss of IFN-γ production by invariant NK T cells in advanced cancer. J. Immunol. 167, 4046-4050.
147. Tallóczy, Z., Jiang, W., Virgin IV, H. W., Leib, D. A., Scheuner, D., Kaufman, R. J., Eskelinen, E-.L. & Levine, B. 2002 Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway. Proc. Natl Acad. Sci. USA 99, 190-195. (doi:10.1073/pnas.012485299.)
148. Taub, J., Lau, J. F., Ma, C., Hahn, J. H., Hoque, R., Rothblatt, J. & Chalfie, M. 1999 A cytosolic catalase is needed to extend adult lifespan in C. elegans darf-C and clk-1 mutants. Nature 399, 162-166. (doi:10.1038/20208.)
149. Tinetti, M. E., Baker, D. J., McAvay, G., Claus, E. B., Garrett, P., Gottschalk, M., Koch, M. L., Trainor, K. & Horwitz, R. I. 1994 A multifactorial intervention to reduce the risk of falling among elderly people in the community. N. Engl. J. Med. 331, 821-827. (doi:10.1056/NEJM199409293311301.)
150. Tran, H., Brunet, A., Griffith, E. C. & Greenberg, M. E. 2003 The many forks in FOXO's road. Sci. STKE, RE5.
151. Traverso, N. et al. 2003 Anti malondialdehyde-adduct immunological response as a possible marker of successful aging. Exp. Gerontol. 38, 1129-1135. (doi:10.1016/S0531-5565(03)00188-8.)
152. Ullum, H., Gøtzsche, P. C., Victor, J., Dickmeiss, E., Skinhøj, P. & Pedersen, K. 1995 Defective natural immunity: an early manifestation of human immunodeficiency virus infection. J. Exp. Med. 182, 789-799. (doi:10.1084/jem.182.3.789.)
153. van der Loo, B., Bachschmid, M., Spitzer, V., Brey, L., Ullrich, V. & Lüscher, T. F. 2003 Decreased plasma and tissue levels of vitamin C in a rat model of aging: implications for antioxidative defense. Biochem. Biophys. Res. Commun. 303, 483-487. (doi:10.1016/S0006-291X(03)00360-7.)
154. +T cell effector function in response to an intracellular pathogen. J. Immunol. 172, 130-137.
155. Vassilakopoulos, T., Karatza, M.-H., Katsaounou, P., Kollintza, A., Zakynthinos, S. & Roussos, C. 2003 Antioxidants attenuate the plasma cytokine response to exercise in humans. J. Appl. Physiol. 94, 1025-1032.
156. Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L. & Müller, F. 2003 Influence of TOR kinase on lifespan in C. elegans. Nature 426, 620. (doi:10.1038/426620a.)
157. Verhasselt, V., Goldman, M. & Willems, F. 1998 Oxidative stress
158. Visser, M., Pahor, M., Taaffe, D. R., Goodpaster, B. H., Simonsick, E. M., Newman, A. B., Nevitt, M. & Harris, T. B. 2002 Relationship of interleukin-6 and tumor necrosis factor-a with muscle mass and muscle strength in elderly men and women: the health ABC study. J. Gerontol. A Biol. Sci. Med. Sci. 57A, M326-M332.
159. Warfield, K. L., Perkins, J. G., Swenson, D. L., Deal, E. M., Bosio, C. M., Aman, M. J., Yokoyama, W. M., Young, H. A. & Bavari, S. 2004 Role of natural killer cells in innate protection against lethal ebola virus infection. J. Exp. Med. 200, 169-179. (doi:10.1084/jem.20032141.)
160. Watanabe, A. et al. 2000 Nutrional therapy of chronic hepatitis by whey protein (non-heated). J. Med. 31, 283-302.
161. Wessells, R. J., Fitzgerald, E., Cypser, J. R., Tatar, M. & Bodmer, R. 2004 Insulin regulation of heart function in aging fruit flies. Nat. Genet. 36, 1275-1281. (doi:10.1038/ng1476.)
162. Wong, C. W. & Watson, D. L. 1995 Immunomodulatory effects of dietary whey proteins in mice. J. Dairy Res. 62, 359-368.
163. Yoshizumi, M., Abe, J., Haendeler, J., Huang, Q. & Berk, B. C. 2000 Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species. J. Biol. Chem. 275, 11 706-11 712. (doi:10.1074/jbc.275.16.11706.)